Herpes virus infections in humans can be caused by different human herpes viruses, the most common being herpes simplex virus types 1 and 2 (HSV1 and HSV2) and varicella-zoster virus (VZV).
Following a primary infection with herpes simplex virus or varicella-zoster virus, the virus establishes latency in the sensory nerve cells for the rest of the patient's life and can subsequently be reactivated repeatedly. Following a reactivation in the nerve cell, the virus is transported through the nerves to the skin and subsequently a lesion develops. One characteristic of herpes virus infection is the inflammation which follows immediately upon an outbreak of virus replication. The inflammation contributes to all symptoms associated with herpes virus recurrence including redness, swelling, itching and pain as well as lesions.
Orofacial lesions, commonly known as fever blisters or cold sores, are caused by HSV1. These lesions most commonly appear on the lips, but may appear on the face, in the mucous membrane lining of the oral cavity, in the eye and nose, and occasionally on the trunk of hands. Infections of the mouth, herpes labialis, are called cold sore (feverblister). Other parts of the face can also be affected and the infections thereof are referred to as facial herpes simplex. The infection can also manifest itself on other parts of the body.
Genital HSV infections are most often caused by HSV-2 and following the primary infection the virus will latently infect sensory or autonomic ganglions. Reactivation will produce the local recurrent lesions on or near the genitals that are characteristic of the herpes infection.
Varicella-zoster virus (VZV) causes varicella, commonly known as chicken pox, and herpes zoster, commonly known as shingles. Shingles affects the skin and nerves and is characterized by groups of small blisters or lesions appearing along certain nerve segments. The lesions are most often seen on the back and may be preceded by a dull ache in the affected site. Pain typically occurs approximately 1 to 3 days before the onset of the rash, but may precede it by a week or more. Once the characteristic unilateral dermatomal rash appears, the diagnosis is almost certain. This rash begins as erythematous macules and papules, which progress first to vesicles (within 12-24 hours), then the pustules (in 3-4 days), and finally to crusts (in 7-10 days).
Once an individual has been infected with the herpes virus, the virus will thereafter remain latently in the body. In latent state, the virus is situated in nerve cell bodies in the ganglia. Due to particular stimuli, such as influenza infection, other respiratory disorders, gastrointestinal infections, stress, fatigue, menstruation, pregnancy, allergy, sunlight, or fever, the latent virus can be activated and travel from the ganglia along the well-defined nerve paths to the skin surface and there multiply and cause the symptoms.
There are a number of antiviral agents which are active against the herpes viruses. Most of the available treatments can only help to accelerate the healing of the lesions and the associated symptoms.
Currently, acyclovir, idoxuridine, famciclovir, vidarabine, foscarnet, valacyclovir, and interferon alpha have all been shown to be efficacious in treating VZV infections. Acyclovir, 9-(2-hydroxyethoxymethyl), Zovirax® Ointment (Glaxo Wellcome), is a purine nucleoside analogue targeting viral encoded DNA polymerase. Other purine nucleoside analogues which are commercially available for treating herpes virus infections include ganciclovir (Roche), penciclovir (Novartis) and foscarnet (Astra). Although effective, these purine nucleoside analogues are poorly soluble in water and demonstrate low bioavailability. These, accompanying the relative long recovery time required (i.e., generally takes longer than 2 weeks for patients to recover).
In the management of pain and discomfort, local anesthetics are widely used. Local anesthetics reversibly block the impulse conduction along nerves and other excitable membranes that primarily utilize sodium channels. Clinically, this action blocks the pain sensation from specific areas of the body.
Among the local anesthetics, lidocaine, 2-(diethylamino)-N-(2,6-dimethylphenyl)-acetamide, is particularly known for its treatment of ventricular tachycardia (an arrythmia of the heart) as an intravenous injection solution. (See e.g., U.S. Pat. No. 3,968,205). Lidocaine is also widely used as a vasoconstrictor to reduce regional blood flow in topical applications or aerosols (such as nasal aerosols to reduce nasal congestion). (See e.g., U.S. Pat. No. 5,534,242). In addition, lidocaine is known for its therapeutic effects in reducing post-herpetic neuralgia (PHN) nerve injury pain from shingles (herpes zoster and post herpetic neuralgia) and analogous neuropathies. For example, U.S. Pat. No. RE37,727 discloses methods employing lidocaine intradermal administration by transport lidocaine from the skin surface, using patches and dressings, into the skin.
There is a great need for effective drugs and methods of treatment for recurrent herpes infections. The present invention addresses this need.